Skip to main content

Advertisement

Log in

The effects of voluntary exercise on learning and memory deficit in Parkinson’s disease model of rats

  • Original Article
  • Published:
Sport Sciences for Health Aims and scope Submit manuscript

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease characterized by progressive and loss of dopaminergic neurons in the SNpc. Behavioral symptoms and cognitive impairments even dementia are common in Parkinson disease. Physical activity impacts functional recovery in humans, however, its effects in experimental animals submitted to Parkinson model have been inconsistent. The present work was focused on the neuroprotective effect of 4 weeks voluntary exercise (wheel running) against experimentally (6-OHDA) induced Parkinson’s disease in rat, by analyzing the memory and learning. Morris water maze test was used for measurement of spatial learning and memory. Results did not demonstrate any main effect differences between the exercise and control groups on weight gain (p > 0.05). 6-OHDA injection caused a significant cognitive deficit in spatial water maze tasks and this effect was reversed in rats after receiving exercise protocol. Voluntary exercise improved the cognitive performance in both reference and working spatial memory against 6-OHDA administration (p < 0.05). We suggest that voluntary exercise interventions may has the potential role in promoting neuroplasticity and repair cognitive dysfunction in Parkinson’s disease (PD).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Miyasaki JM et al (2006) Practice Parameter: Evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 66(7):996–1002

    Article  CAS  PubMed  Google Scholar 

  2. De Rijk Md et al (1997) Prevalence of parkinsonism and Parkinson’s disease in Europe: the EUROPARKINSON Collaborative Study. European Community Concerted Action on the Epidemiology of Parkinson’s disease. J Neurol Neurosurg Psychiatry 62(1):10–15

    Article  PubMed  PubMed Central  Google Scholar 

  3. Fahn S (2003) Description of Parkinson’s disease as a clinical syndrome. Ann N Y Acad Sci 991(1):1–14

    Article  CAS  PubMed  Google Scholar 

  4. Sethi KD (2002) Clinical aspects of Parkinson disease. Curr Opin Neurol 15:457–460

    Article  PubMed  Google Scholar 

  5. Carbon M, Marié RM (2003) Functional imaging of cognition in Parkinson’s disease. Curr Opin Neurol 16(4):475–480

    PubMed  Google Scholar 

  6. Witt K, Nuhsman A, Deuschl G (2002) Dissociation of habit-learning in Parkinson’s and cerebellar disease. J Cogn Neurosci 14(3):493–499

    Article  CAS  PubMed  Google Scholar 

  7. Lewis SJ, Slabosz A, Robbins TW, Barker RA, Owen AM (2005) Dopaminergic basis for deficits in working memory but not attentional set-shifting in Parkinson’s disease. Neuropsychologia 43(6):823–832

    Article  PubMed  Google Scholar 

  8. Ang ET, Gomez-Pinilla F (2007) Potential therapeutic effects of exercise to the brain. Curr Med Chem 14:2564–2571

    Article  CAS  PubMed  Google Scholar 

  9. van Praag H, Christie BR, Sejnowski TJ, Gage FH (1999) Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci USA 96:13427–13431

    Article  PubMed  Google Scholar 

  10. Tillerson JL, Caudle WM, Reveron ME, Miller GW (2003) Exercise induces behavioral recovery and attenuates neurochemical deficits in rodent models of Parkinson’s disease. Neuroscience 119:899–911

    Article  CAS  PubMed  Google Scholar 

  11. Petzinger GM et al (2013) Exercise-enhanced neuroplasticity targeting motor and cognitive circuitry in Parkinson’s disease. Lancet Neurol 12(7):716–726

    Article  PubMed  PubMed Central  Google Scholar 

  12. Goodwin VA, Richards SH, Taylor RS, Taylor AH, Campbell JL (2008) The effectiveness of exercise interventions for people with Parkinson’s disease: a systematic review and meta-analysis. Mov Disord 23:631–640

    Article  PubMed  Google Scholar 

  13. Julien C et al (2006) Postmortem brain fatty acid profile of levodopa-treated Parkinson disease patients and parkinsonian monkeys. Neurochem Int 48(5):404–414

    Article  CAS  PubMed  Google Scholar 

  14. Samadi P et al (2006) Docosahexaenoic acid reduces levodopa-induced dyskinesias in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine monkeys. Ann Neurol 59(2):282–288

    Article  CAS  PubMed  Google Scholar 

  15. Schapira AH et al (2006) Novel pharmacological targets for the treatment of Parkinson’s disease. Nat Rev Drug Discov 5(10):845–854

    Article  CAS  PubMed  Google Scholar 

  16. Kim D-H et al (2010) Treadmill exercise inhibits traumatic brain injury-induced hippocampal apoptosis. Physiol Behav 101(5):660–665

    Article  CAS  PubMed  Google Scholar 

  17. Kim S-E et al (2010) Treadmill exercise prevents aging-induced failure of memory through an increase in neurogenesis and suppression of apoptosis in rat hippocampus. Exp Gerontol 45(5):357–365

    Article  PubMed  Google Scholar 

  18. Bove J, Perier C (2012) Neurotoxin-based models of Parkinson’s disease. Neuroscience 211:51–76

    Article  CAS  PubMed  Google Scholar 

  19. Farbood Y et al (2015) Ellagic acid protects the brain against 6-hydroxydopamine induced neuroinflammation in a rat model of Parkinson’s disease. Basic Clin Neurosci 6(2):83–90

    PubMed  PubMed Central  Google Scholar 

  20. Rafie F, Shabazi M, Sheikh M, Naghdi N, Sheibani V (2017) Effects of voluntary exercise on motor function in Parkinson’s disease model of rats. Ann Appl Sport Sci 5(2):81–86

    Article  Google Scholar 

  21. Da Cunha C, Angelucci ME, Canteras NS, Wonnacott S, Takahashi RN (2002) The lesion of the rat substantia nigra pars compacta dopaminergic neurons as a model for Parkinson’s disease memory disabilities. Cell Mol Neurobiol 22(3):227–237

    Article  PubMed  Google Scholar 

  22. Salari M, Sheibani V, Saadati H, Pourrahimi A, Esmaeelpour K, Khodamoradi M (2015) The compensatory effect of regular exercise on long-term memory impairment in sleep deprived female rats. Behav Process 119:50–57

    Article  Google Scholar 

  23. Schrag A, Jahanshahi M, Quinn N (2000) What contributes to quality of life in patients with Parkinson’s disease? J Neurol Neurosurg Psychiatry 69(3):308–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gorton LM et al (2010) Exercise effects on motor and affective behavior and catecholamine neurochemistry in the MPTP-lesioned mouse. Behav Brain Res 213(2):253–262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Howells FM et al (2005) Stress reduces the neuroprotective effect of exercise in a rat model for Parkinson’s disease. Behav Brain Res 165(2):210–220

    Article  CAS  PubMed  Google Scholar 

  26. Nieuwboer A et al (2009) Motor learning in Parkinson’s disease: limitations and potential for rehabilitation. Parkinsonism Relat Disord 15:S53–S58 (48)

    Article  PubMed  Google Scholar 

  27. Sheibani V, Rafie F, Shahbazi M, Naghdi N, Sheikh M (2017) Comparison of voluntary and forced exercise effects on motor behavior in 6-hydroxydopamine-lesion rat model of Parkinson’s disease. Sport Sci Health 13(1):203–211

    Article  Google Scholar 

  28. Hayes K et al (2008) Forced, not Voluntary exercise effectively induces neuroprotection in stroke. Acta Neuropathol 115:289–296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kinni H et al (2011) Cerebral metabolism after forced or voluntary physical exercise. Brain Res 1388:48–55

    Article  CAS  PubMed  Google Scholar 

  30. Lambert M et al (1996) Tests of running performance do not predict subsequent spontaneous running in rats. Physiol Behav 60(1):171–176

    Article  CAS  PubMed  Google Scholar 

  31. Tarr BA et al (2004) Voluntary running distance is negatively correlated with striatal dopamine release in untrained rats. Behav Brain Res 154(2):493–499

    Article  CAS  PubMed  Google Scholar 

  32. Ferro MM, Bellissimo MI, Anselmo-Franci JA, Angellucci ME, Canteras NS, Da Cunha C (2005) Comparison of bilaterally 6-OHDA-and MPTP-lesioned rats as models of the early phase of Parkinson’s disease: histological, neurochemical, motor and memory alterations. J Neurosci Methods 148(1):78–87

    Article  CAS  PubMed  Google Scholar 

  33. Sconce MD, Churchill MJ, Greene RE, Meshul CK (2015) Intervention with exercise restores motor deficits but not nigrostriatal loss in a progressive MPTP mouse model of Parkinson’s disease. Neuroscience 299:156–174

    Article  CAS  PubMed  Google Scholar 

  34. Braak H, Rüb U, Steur EJ, Del Tredici K, De Vos RA (2005) Cognitive status correlates with neuropathologic stage in Parkinson disease. Neurology 64(8):1404–10

    Article  CAS  PubMed  Google Scholar 

  35. Murray DK, Sacheli MA, Eng JJ, Stoessl AJ (2014) The effects of exercise on cognition in Parkinson’s disease: a systematic review. Transl Neurodegen 3(1):1

    Article  Google Scholar 

  36. García-Capdevila S, Portell-Cortés I, Torras-Garcia M, Coll-Andreu M, Costa-Miserachs D (2009) Effects of long-term voluntary exercise on learning and memory processes: dependency of the task and level of exercise. Behav Brain Res 202(2):162–170

    Article  PubMed  Google Scholar 

  37. Cotman CW, Engesser-Cesar C (2002) Exercise enhances and protects brain function. Exerc Sport Sci Rev 30(2):75–79

    Article  PubMed  Google Scholar 

  38. Crowley EK, Nolan YM, Sullivan AM (2018) Neuroprotective effects of voluntary running on cognitive dysfunction in an α-synuclein rat model of Parkinson’s disease. Neurobiol Aging 65:60–68

    Article  CAS  PubMed  Google Scholar 

  39. Paillard T, Rolland Y, de Souto Barreto P (2015) Protective effects of physical exercise in Alzheimer’s disease and Parkinson’s disease: a narrative review. J Clin Neurol 11(3):212–219

    Article  PubMed  PubMed Central  Google Scholar 

  40. Alomari MA, Khabour OF, Alzoubi KH, Alzubi MA (2016) Combining restricted diet with forced or voluntary exercises improves hippocampal BDNF and cognitive function in rats. Int J Neurosci 126(4):366–373

    Article  CAS  PubMed  Google Scholar 

  41. Vučcković MG, Li Q, Fisher B, Nacca A et al (2010) Exercise elevates dopamine D2 receptor in a mouse model of Parkinson’s disease: in vivo imaging with (18F) fallypride. Mov Disord 25(16):2777–2784

    Article  Google Scholar 

  42. Mabandla M, Kellaway L, Gibson ASC, Russell VA (2004) Voluntary running provides neuroprotection in rats after 6-hydroxydopamine injection into the medial forebrain bundle. Metab Brain Dis 19(1–2):43–50

    Article  CAS  PubMed  Google Scholar 

  43. Aguiar AS, Castro AA, Moreira EL, Glaser V et al (2011) Short bouts of mild-intensity physical exercise improve spatial learning and memory in aging rats: involvement of hippocampal plasticity via AKT, CREB and BDNF signaling. Mech Ageing Dev 132(11):560–567

    Article  CAS  PubMed  Google Scholar 

  44. Zang J, Liu Y, Li W, Xiao D, Zhang Y, Luo Y, Liang W, Liu F, Wei W (2017) Voluntary exercise increases adult hippocampal neurogenesis by increasing GSK-3β activity in mice. Neuroscience 354:122–135

    Article  CAS  PubMed  Google Scholar 

  45. Zhou W, Barkow JC, Freed CR (2017) Running wheel exercise reduces α-synuclein aggregation and improves motor and cognitive function in a transgenic mouse model of Parkinson’s disease. PloS One 12(12):e0190160

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank the Neuroscience Research Center of Kerman, Iran for financial support; Dr. Khadije Esmaeilpoue and Dr. Sina Kakoei for their technical assistance in this project.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to F. Rafie.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All experiments were performed in accordance with the National Institutes of Health ‘Guide for the Care and Use of Laboratory Animals’ and approved by the Ethics Committee of Kerman Neuroscience Research Center.

Informed consent

For this type of study the formal informed consent is not requried.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rafie, F., Sheibani, V., Shahbazi, M. et al. The effects of voluntary exercise on learning and memory deficit in Parkinson’s disease model of rats. Sport Sci Health 15, 399–405 (2019). https://doi.org/10.1007/s11332-019-00531-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11332-019-00531-7

Keywords

Navigation